Orthotopic liver transplantation will be used to treat between twenty-five and thirty patients per year with end-stage non-neoplastic liver disease. To identify appropriate candidates, a national network of collaborating universities has been established. From observations of these patients after transplantation, it is hoped to provide more decisive guidelines for the differential diagnosis of graft rejection, biliary obstruction, hepatitis and other causes of hepatic malfunction in the postoperative period. Sequential in vitro studies of immunologic reactivity will be carried out, including an assessment of cell mediated immunity and humoral antibody effects. The influence of pre-existing liver disease upon the outcome after hepatic replacement will be determined, as well as the effects of hepatic replacement upon the recovery of other secondarily affected organs including the kidney and brain. Inborn errors of metabolism will be considered as indications for transplantation, including Wilson's Disease, some of the glycogen storage diseases, and alpha-1 anti-Trypsin deficiency, to mention only three. Observations will be made upon the carbohydrate, lipid and protein metabolism in the liver recipients. From this work, an attempt will be made to more precisely define the role of orthotopic liver transplantation in the field of human hepatology.